Prostate cancer is the most commonly diagnosed malignancy in United States males, and is the second leading cause of male cancer deaths in the U.S. (Feuer et al., 1999). As medical care and overall health lead to increases in the age of the male population, so too will the incidence of prostate cancer. As such, the prevention of prostate cancer is of national medical concern. While surgery, radiotherapy and androgen ablation therapy of prostate cancer is available for the treatment of the disease at an early stage, no effective therapy is currently available against the advanced metastatic disease.
Antitumor antibiotics have been the focus of recent cancer research. Most of these antibiotics kill cells by interacting with cellular DNA inducing DNA cross-linking and strand breaks, as well as by activiating cellular apoptotic machinery. Recently, a new antitumor antibiotic, leinamycin (LNM) has shown potency in various murine tumor models. LNM exerts its cytoxicity by a thio-dependent, alkylative DNA cleavage mediated by an episulfonium ion intermediate. Although LNM appears to be more effective at killing tumor cells, the mode of activation for LNM requires a reductive environment.
While most cancer cells are under hypoxic conditions (ideal for reductive activation), prostate cancer cells are unique in such that they are under high oxidative stress. The oxidative environment of prostate cancer cells might be one of the reasons that renders clinically important anticancer drugs that require reductive active activation ineffective. Thus, in view of the oxidative environment of prostate cancer cells, the generation of LNM antibiotics may not be as effective, thus, there is still a need for an effective antitumor antibiotic to treat prostate cancer.